Heart transplantation(HTx)is a life-saving procedure for patients with end-stage heart failure and has undergone remarkable advancements since the first succe-ssful transplant in 1967.The introduction of cyclosporine ...Heart transplantation(HTx)is a life-saving procedure for patients with end-stage heart failure and has undergone remarkable advancements since the first succe-ssful transplant in 1967.The introduction of cyclosporine in the 1970s significantly improved patient outcomes,leading to a global increase in transplants,including in India,where the practice has grown despite initial challenges.This review pro-vides an extensive overview of HTx,focusing on current practices,technological advancements,and the ongoing challenges the field faces today.It explores the evolution of surgical techniques,such as minimally invasive and robotic-assisted procedures,and the management of posttransplant rejection through tailored immunosuppressive strategies,including new monoclonal antibodies and perso-nalized therapies.The review also highlights emerging innovations such as mechanical circulatory support devices and xenotransplantation as potential solutions to donor shortages while acknowledging the ethical and logistical challenges these approaches entail.Furthermore,the analysis delves into the implications of using extended-criteria donors and the role of multidisciplinary teams in evaluating absolute and relative contraindications.Despite the progress made,the persistent issues of organ scarcity and ethical concerns underscore the need for ongoing research and innovation to further enhance the efficacy,safety,and accessibility of HTx.展开更多
The brain is the most complex human organ,and commonly used models,such as two-dimensional-cell cultures and animal brains,often lack the sophistication needed to accurately use in research.In this context,human cereb...The brain is the most complex human organ,and commonly used models,such as two-dimensional-cell cultures and animal brains,often lack the sophistication needed to accurately use in research.In this context,human cerebral organoids have emerged as valuable tools offering a more complex,versatile,and human-relevant system than traditional animal models,which are often unable to replicate the intricate architecture and functionality of the human brain.Since human cerebral organoids are a state-of-the-art model for the study of neurodevelopment and different pathologies affecting the brain,this field is currently under constant development,and work in this area is abundant.In this review,we give a complete overview of human cerebral organoids technology,starting from the different types of protocols that exist to generate different human cerebral organoids.We continue with the use of brain organoids for the study of brain pathologies,highlighting neurodevelopmental,psychiatric,neurodegenerative,brain tumor,and infectious diseases.Because of the potential value of human cerebral organoids,we describe their use in transplantation,drug screening,and toxicology assays.We also discuss the technologies available to study cell diversity and physiological characteristics of organoids.Finally,we summarize the limitations that currently exist in the field,such as the development of vasculature and microglia,and highlight some of the novel approaches being pursued through bioengineering.展开更多
The growth,survival,and mortality of conifer species in response to the hydrothermal regime have received considerable attention.It is expected that the highest sensitivity of trees to the warming-drying climate will ...The growth,survival,and mortality of conifer species in response to the hydrothermal regime have received considerable attention.It is expected that the highest sensitivity of trees to the warming-drying climate will occur mainly at the edges of the species ranges.We focused on the responses to climate change of the drought-resistant larch(Larix sibirica)and the moisture-sensitive Siberian pine(Pinus sibirica)along the elevation gradient in the Tannu-Ola Ridge,the southern margin where those two species coexist in Siberia by using satellite data(MODIS,Landsat,and microwave),the indexes of gross(GPP)and net(NPP)primary productivity,and tree radial growth index(GI).We found that since the warming restart in the 2000s,the area of larch-dominated forests increased by~150%while the area of pine-dominated forests decreased by~10%.The Siberian pine has retreated at low elevations(<1800 m)and increased its area at higher ones.In contrast,the area of larch stands increased in both the uphill and downhill directions.Birch(Betula spp.)also increased its area at low elevations(about+120%).Since 2001,the forested area increased by~5%.A shrubification,i.e.,an increase in the area of shrubs,was observed at high elevations.The uphill rate of timberline and shrubline migration was about 0.3 m/a.Since the 2000s,vegetation NPP has increased by 13%.A notable correlation between NPP and the GI of larch and pine was found(r=0.5-0.7).At lower elevations,NPP positively correlated with precipitation and soil moisture,while air temperature and VPD(vapor pressure deficit)increase inhibited productivity.At high elevations,the effects of these variables on productivity reversed.The continuous decline of the Siberian pine forest indicates an inevitable retreat of this species at low elevations and its replacement by larch and birch.展开更多
Automated and accurate movie genre classification is crucial for content organization,recommendation systems,and audience targeting in the film industry.Although most existing approaches focus on audiovisual features ...Automated and accurate movie genre classification is crucial for content organization,recommendation systems,and audience targeting in the film industry.Although most existing approaches focus on audiovisual features such as trailers and posters,the text-based classification remains underexplored despite its accessibility and semantic richness.This paper introduces the Genre Attention Model(GAM),a deep learning architecture that integrates transformer models with a hierarchical attention mechanism to extract and leverage contextual information from movie plots formulti-label genre classification.In order to assess its effectiveness,we assessmultiple transformer-based models,including Bidirectional Encoder Representations fromTransformers(BERT),ALite BERT(ALBERT),Distilled BERT(DistilBERT),Robustly Optimized BERT Pretraining Approach(RoBERTa),Efficiently Learning an Encoder that Classifies Token Replacements Accurately(ELECTRA),eXtreme Learning Network(XLNet)and Decodingenhanced BERT with Disentangled Attention(DeBERTa).Experimental results demonstrate the superior performance of DeBERTa-based GAM,which employs a two-tier hierarchical attention mechanism:word-level attention highlights key terms,while sentence-level attention captures critical narrative segments,ensuring a refined and interpretable representation of movie plots.Evaluated on three benchmark datasets Trailers12K,Large Movie Trailer Dataset-9(LMTD-9),and MovieLens37K.GAM achieves micro-average precision scores of 83.63%,83.32%,and 83.34%,respectively,surpassing state-of-the-artmodels.Additionally,GAMis computationally efficient,requiring just 6.10Giga Floating Point Operations Per Second(GFLOPS),making it a scalable and cost-effective solution.These results highlight the growing potential of text-based deep learning models in genre classification and GAM’s effectiveness in improving predictive accuracy while maintaining computational efficiency.With its robust performance,GAM offers a versatile and scalable framework for content recommendation,film indexing,and media analytics,providing an interpretable alternative to traditional audiovisual-based classification techniques.展开更多
The Rh blood group system,especially the D antigen,is crucial in transfusion medicine and obstetrics.Weak D phenotypes,caused by mutations in the Rhesus D antigen(RhD)blood group(RHD)gene,result in reduced antigen exp...The Rh blood group system,especially the D antigen,is crucial in transfusion medicine and obstetrics.Weak D phenotypes,caused by mutations in the Rhesus D antigen(RhD)blood group(RHD)gene,result in reduced antigen expression,posing challenges in serological testing and clinical management.Variability in detection methods leads to inconsistent results,making accurate classification difficult.Molecular techniques like polymerase chain reaction and DNA sequencing have significantly improved the identification of weak D variants,offering more reliable transfusion strategies and reducing the risk of alloimmunization.However,challenges such as lack of standardized protocols,cost constraints,and population-specific variations remain.In obstetrics,proper management of pregnant women with weak D is essential to prevent hemolytic disease of the fetus and newborn.Non-invasive prenatal testing using cell-free fetal DNA shows promise in predicting RhD incompatibility and minimizing unnecessary Rh immune globulin administration.Future advancements in highthroughput genotyping and discovery of novel RHD alleles could enhance RhD testing accuracy and efficiency.Standardizing RHD genotyping and adopting genotype-based management strategies for Rh immune globulin therapy and red blood cell transfusions will improve patient safety and clinical outcomes.This review examines the molecular basis,challenges,and future prospects in weak D phenotype management.展开更多
Extracorporeal liver surgery(ELS), also known as liver autotransplantation, is a hybrid(cross-fertilized) surgery incorporating the technical knowledge from extreme liver and transplant liver surgeries, and recently b...Extracorporeal liver surgery(ELS), also known as liver autotransplantation, is a hybrid(cross-fertilized) surgery incorporating the technical knowledge from extreme liver and transplant liver surgeries, and recently became more embraced and popularized among leading centers. ELS could be summarized into three major categories, namely, ex-situ liver resection and autotransplantation(ELRA), ante-situm liver resection and autotransplantation(ALRA) and auxiliary partial liver autotransplantation(APLA). The successful development of ELS during the past 37 years is definitely inseparable from continuous effort s done by Chinese surgeons and researchers. Especially, the precision liver surgery paradigm has allowed to transform ELS into a modularized, more simplified, and standardized surgery, to upgrade surgical skills, to improve peri-operative outcome and long-term survival, to increase the capability of surgeons to select more complex diseases and to expand the level of medical service to the population. This review highlights the Chinese contributions to the field of ELS, focusing thereby on features of different surgical types, technical innovations, disease selection and surgical indication, patient prognosis and future perspectives.展开更多
Global climate change has become one of the most pressing challenges of the 21st century.As anthropogenic CO_(2) emissions from fossil fuel consumption and industrial processes continue to disrupt Earth’s carbon cycl...Global climate change has become one of the most pressing challenges of the 21st century.As anthropogenic CO_(2) emissions from fossil fuel consumption and industrial processes continue to disrupt Earth’s carbon cycle,atmospheric CO_(2) concentrations have reached unprecedented levels-exceeding 420 parts per million(ppm)in 2023 compared to pre-industrial 280 ppm.This rapid accumulation of greenhouse gases has resulted in measurable con-sequences including rising global temperatures,ocean acidifica-tion,and increased frequency of extreme weather events.展开更多
Lynch syndrome(LS),also known as hereditary non-polyposis colorectal cancer(HNPCC),is an inherited condition associated with a higher risk of colorectal cancer(CRC)and other cancers.It is caused by germline mutations ...Lynch syndrome(LS),also known as hereditary non-polyposis colorectal cancer(HNPCC),is an inherited condition associated with a higher risk of colorectal cancer(CRC)and other cancers.It is caused by germline mutations in DNA mismatch repair(MMR)genes,including MLH1,MSH2,MSH6 and PMS2.These mutations lead to microsatellite instability(MSI)and defective DNA repair mechanisms,resulting in increased cancer risk.Early detection of LS is crucial for effective management and cancer prevention.Endoscopic surveillance,particularly regular colonoscopy,is recommended for individuals with LS to detect CRC at early stages.Additionally,universal screening of CRC for MMR deficiency can help identify at-risk individuals.Genetic counseling plays a valuable role in LS by guiding patients and their families in understanding the genetic basis,making informed decisions regarding surveillance and prevention,and offering reproductive options to reduce the transmission of pathogenic variants of the offspring.The aim of this review is to outline current strategies for the diagnosis,surveillance,and management of LS,with a focus on the role of genetic counseling,endoscopic screening,and emerging therapeutic approaches to mitigate cancer risk in affected individuals.展开更多
In this letter,a commentary on the article by Xu et al has been provided.Gastrointestinal stomal tumours(GISTs)are rare tumours that originate commonly in stomach(60%-70%)and small intestine(30%-40%).The course of tre...In this letter,a commentary on the article by Xu et al has been provided.Gastrointestinal stomal tumours(GISTs)are rare tumours that originate commonly in stomach(60%-70%)and small intestine(30%-40%).The course of treatment especially oesophageal GIST is very complex and hard to diagnose because of limited availability of pathological and clinical data.Endoscopic resection(ER)is a minimally invasive approach for removing tumours from the oesophagus and digestive system that does not require open surgery and is especially successful for very small and low-risk GIST.A retrospective exami-nation of 32 patients treated with ER between 2012 and 2023 was conducted to analyse clinical and pathological characteristics,effectiveness of therapy,and long-term prognosis.The findings demonstrate en bloc resection was achieved in 96.9%of cases with an R0 resection rate of 75%with a median size of tumour was approximately 2.12 cm.Post-surgery complication like hydrothorax,post-endoscopic submucosal dissection electrocoagulation syndrome occurred in about 25%of cases which later go resolved by conservative treatment.Recurrence of GIST was approximately 9.4%primarily in high-risk cases.ER should be widely adopted in clinical practise preferably for managing low-risk oesophageal GIST because of its high success rate,low recurrence rates and excellent survival results,ensuring better patient prognosis.展开更多
The pursuit of alternative fuel generation technologies has gained momentum due to the diminishing reserves of fossil fuels and global warming from increased CO_(2)emission.Among the proposed methods,the hydrogenation...The pursuit of alternative fuel generation technologies has gained momentum due to the diminishing reserves of fossil fuels and global warming from increased CO_(2)emission.Among the proposed methods,the hydrogenation of CO_(2)to produce marketable carbon-based products like methanol and ethanol is a practical approach that offers great potential to reduce CO_(2)emissions.Although significant volumes of methanol are currently produced from CO_(2),developing highly efficient and stable catalysts is crucial for further enhancing conversion and selectivity,thereby reducing process costs.An in-depth examination of the differences and similarities in the reaction pathways for methanol and ethanol production highlights the key factors that drive C-C coupling.Identifying these factors guides us toward developing more effective catalysts for ethanol synthesis.In this paper,we explore how different catalysts,through the production of various intermediates,can initiate the synthesis of methanol or ethanol.The catalytic mechanisms proposed by spectroscopic techniques and theoretical calculations,including operando X-ray methods,FTIR analysis,and DFT calculations,are summarized and presented.The following discussion explores the structural properties and composition of catalysts that influence C-C coupling and optimize the conversion rate of CO_(2)into ethanol.Lastly,the review examines recent catalysts employed for selective methanol and ethanol production,focusing on single-atom catalysts.展开更多
Variation in the vocal behavior of nonhuman vertebrates includes graded transitions and more dramatic changes.Wapiti males produce a reproductive bugle that has a fundamental frequency that surpasses 2,000 Hz with evi...Variation in the vocal behavior of nonhuman vertebrates includes graded transitions and more dramatic changes.Wapiti males produce a reproductive bugle that has a fundamental frequency that surpasses 2,000 Hz with evidence of biphonation and other nonlinear phenomena.Here,we analyze the acoustic structure of captive wapiti vocalizations to compare the male bugle with 3 categories of distress vocalizations:neonate distress(capture)calls,calf isolation calls,and adult female isolation calls.These 4 high-arousal call categories serve a common general function in recruiting conspecifics but occur in different behavioral contexts(capture,isolation,reproduction).Our goal was to distinguish characteristics that vary in graded steps that may correspond to an animal’s age or size from characteristics that are unique to the bugle.Characteristics of the high and loud fundamental(G0)varied in an age/size-graded manner with a decrease in minimum G0,an increase in the maximum and range of G0,with no evidence of sex differences.The nonlinear phenomena of deterministic chaos,biphonation,and frequency jumps were present in all 4 call categories and became more common from the distress vocalizations of neonates to calves to adult females to the male bugle.Two temporal characteristics sharply distinguished the bugle from the 3 categories of distress vocalizations:these included a prolonged call duration and a maximum G0 that occurred much later in the call for the bugle than for distress vocalizations.Our results suggest that distress vocalizations of different age groups and the reproductive bugle of wapiti share a high G0,with age/size-graded changes in G0 and nonlinear phenomena,but differ sharply in temporal characteristics.展开更多
Selfishness,understood as excessive focus on the self,appears to be a predominant feature of contemporary culture.While the degree of self-focus is adaptive for survival and decision-making,self-rigidity has been asso...Selfishness,understood as excessive focus on the self,appears to be a predominant feature of contemporary culture.While the degree of self-focus is adaptive for survival and decision-making,self-rigidity has been associated with significant psychological,interpersonal,and social costs.Throughout history,philosophers,religious leaders,and social activists have promoted a“hypo-egoic”way of being,characterized by reduced self-fixation and greater openness to others.However,a key question arises:How can one cultivate a more flexible and interdependent perspective on the self?Deconstructive meditations are a group of contemplative practices that aim to dismantle self-rigidity by exploring perception,cognition,and emotion.Their central mechanism is self-inquiry,an experiential process that involves directly observing patterns of the self,questioning the solidity of identity,and developing new ways to relate to experience.From the perspective of contemplative neuroscience,these practices have been shown to reduce selfnarrative identification and promote psychological flexibility.Despite their potential,empirical research on deconstructive meditations remains limited and requires further investigation.This article reviews the essential findings on practices,their connection to psychotherapy,and their potential therapeutic applications.Finally,their clinical implications are discussed along with future research directions to validate their impact on mental health.展开更多
BACKGROUND The rising global prevalence of gastroesophageal reflux disease(GERD)has been closely linked to lifestyle changes driven by globalization.GERD imposes a substantial public health burden,affecting quality of...BACKGROUND The rising global prevalence of gastroesophageal reflux disease(GERD)has been closely linked to lifestyle changes driven by globalization.GERD imposes a substantial public health burden,affecting quality of life and leading to potential complications.Early intervention through lifestyle modification can prevent disease onset;however,there is a lack of effective risk prediction models that emphasize primary prevention.AIM To develop and validate a GERD Risk Scoring System(GRSS)aimed at identifying high-risk individuals and promoting primary prevention strategies.METHODS A 45-item questionnaire encompassing major lifestyle and demographic risk factors was developed and validated.It was administered to healthy controls and GERD patients.Two regression models-one using continuous variables and another using categorized variables-were used to develop a computational prediction equation and a clinically applicable scoring scale.An independent validation cohort of 355 participants was used to assess model performance in terms of discrimination(C-index),calibration,sensitivity,specificity,internal consistency(Cronbach's alpha),and test-retest reliability(intraclass correlation coefficient,Bland-Altman analysis).RESULTS Significant associations were observed between GERD and key lifestyle factors.The derived GRSS equation and scoring scale demonstrated strong discriminative ability,with high sensitivity and specificity.The scoring system exhibited excellent internal consistency(Cronbach’s alpha)and strong test-retest reliability.The C-index indicated excellent predictive accuracy in both derivation and validation cohorts.CONCLUSION GRSS offers a novel and validated approach to GERD risk prediction,combining a robust equation for digital applications and a practical scale for clinical use.Its ability to accurately identify at-risk individuals supports a paradigm shift toward primary prevention,underscoring its significance in addressing the growing burden of GERD at the population level.展开更多
Conventional soil maps(CSMs)often have multiple soil types within a single polygon,which hinders the ability of machine learning to accurately predict soils.Soil disaggregation approaches are commonly used to improve ...Conventional soil maps(CSMs)often have multiple soil types within a single polygon,which hinders the ability of machine learning to accurately predict soils.Soil disaggregation approaches are commonly used to improve the spatial and attribute precision of CSMs.The approach disaggregation and harmonization of soil map units through resampled classification trees(DSMART)is popular but computationally intensive,as it generates and assigns synthetic samples to soil series based on the areal coverage information of CSMs.Alternatively,the disaggregation approach pure polygon disaggregation(PPD)assigns soil series based solely on the proportions of soil series in pure polygons in CSMs.This study compared these two disaggregation approaches by applying them to a CSM of Middlesex County,Ontario,Canada.Four different sampling methods were used:two sampling designs,simple random sampling(SRS)and conditional Latin hypercube sampling(cLHS),with two sample sizes(83100 and 19420 samples per sampling plan),both based on an area-weighted approach.Two machine learning algorithms(MLAs),C5.0 decision tree(C5.0)and random forest(RF),were applied to the disaggregation approaches to compare the disaggregation accuracy.The accuracy assessment utilized a set of 500 validation points obtained from the Middlesex County soil survey report.The MLA C5.0(Kappa index=0.58–0.63)showed better performance than RF(Kappa index=0.53–0.54)based on the larger sample size,and PPD with C5.0 based on the larger sample size was the best-performing(Kappa index=0.63)approach.Based on the smaller sample size,both cLHS(Kappa index=0.41–0.48)and SRS(Kappa index=0.40–0.47)produced similar accuracy results.The disaggregation approach PPD exhibited lower processing capacity and time demands(1.62–5.93 h)while yielding maps with lower uncertainty as compared to DSMART(2.75–194.2 h).For CSMs predominantly composed of pure polygons,utilizing PPD for soil series disaggregation is a more efficient and rational choice.However,DSMART is the preferable approach for disaggregating soil series that lack pure polygon representations in the CSMs.展开更多
Dental implants have restored masticatory function to over 100000000 individuals,yet almost 1000000 implants fail each year due to peri-implantitis,a disease triggered by peri-implant microbial dysbiosis.Our ability t...Dental implants have restored masticatory function to over 100000000 individuals,yet almost 1000000 implants fail each year due to peri-implantitis,a disease triggered by peri-implant microbial dysbiosis.Our ability to prevent and treat peri-implantitis is hampered by a paucity of knowledge of how these biomes are acquired and the factors that engender normobiosis.Therefore,we combined a 3-month interventional study of 15 systemically and periodontally healthy adults with whole genome sequencing,finescale enumeration and graph theoretics to interrogate colonization dynamics in the pristine peri-implant sulcus.We discovered that colonization trajectories of implants differ substantially from adjoining teeth in acquisition of new members and development of functional synergies.Source-tracking algorithms revealed that this niche is initially seeded by bacteria trapped within the coverscrew chamber during implant placement.These pioneer species stably colonize the microbiome and exert a sustained influence on the ecosystem by serving as anchors of influential hubs and by providing functions that enable cell replication and biofilm maturation.Unlike the periodontal microbiome,recruitment of new members to the peri-implant community occurs on nepotistic principles.Maturation is accompanied by a progressive increase in anaerobiosis,however,the predominant functionalities are oxygen-dependent over the 12-weeks.The peri-implant community is easily perturbed following crown placement,but demonstrates remarkable resilience;returning to pre-perturbation states within three weeks.This study highlights important differences in the development of the periodontal and peri-implant ecosystems,and signposts the importance of placing implants in periodontally healthy individuals or following the successful resolution of periodontal disease.展开更多
Aortic regurgitation(AR)poses distinct challenges in interventional cardiology,necessitating novel approaches for treatment.This editorial examined the evolving landscape of transcatheter aortic valve replacement(TAVR...Aortic regurgitation(AR)poses distinct challenges in interventional cardiology,necessitating novel approaches for treatment.This editorial examined the evolving landscape of transcatheter aortic valve replacement(TAVR)as an alternative therapeutic strategy for AR,particularly in patients deemed high risk for surgery.We explored the anatomical and patho-physiological disparities between AR and aortic stenosis(AS)and elucidates the technical nuances of TAVR procedures in AR pa-tients,emphasizing the need for precise prosthesis positioning and considerations for excessive stroke volume.Additionally,we discussed the safety and efficacy of TAVR compared to SAVR in AR management,drawing insights from recent case series and registry data.Notably,dedicated TAVR devices tailored for AR,such as the J-Valve and JenaValve,demonstrate promising out-comes in reducing residual AR and ensuring procedural success.Conversely,“off-label”TAVR devices,including balloon-ex-pandable and self-expandable platforms,offer feasible alternatives-particularly for large aortic annuli-with favorable device suc-cess rates and low residual AR rates.We highlighted the need for further research,including randomized trials,to delineate the definitive role of TAVR in AR treatment and to address remaining questions regarding device selection and long-term outcomes.In conclusion,TAVR emerges as a viable option for patients with AR,particularly those facing high surgical risks or frailty,with ongoing investigations poised to refine its position in the therapeutic armamentarium.展开更多
Suicide is defined as the act of a person attempting to take their own life by causing death.Suicide is a complex phenomenon that is influenced by a multitude of factors,including psychosocial,cultural,and religious a...Suicide is defined as the act of a person attempting to take their own life by causing death.Suicide is a complex phenomenon that is influenced by a multitude of factors,including psychosocial,cultural,and religious aspects,as well as genetic,biochemical,and environmental factors.From a biochemical perspective,it is crucial to consider the communication between the endocrine,immune,and nervous systems when studying the etiology of suicide.Several pathologies involve the bidirectional communication between the peripheral activity and the central nervous system by the action of molecules such as cytokines,hormones,and neurotransmitters.These humoral signals,when present in optimal quantities,are responsible for maintaining physiological homeostasis,including mood states.Stress elevates the cortisol and proinflammatory cytokines levels and alter neurotransmitters balance,thereby increasing the risk of developing a psychiatric disorder and subsequently the risk of suicidal behavior.This review provides an integrative perspective about the neurochemical,immunological,and endocrinological disturbances associated with suicidal behavior,with a particular focus on those alterations that may serve as potential risk markers and/or indicators of the state preceding such a tragic act.展开更多
Objective:To characterize the pediatric population with cutaneous leishmaniasis treated at a research center and to determine the therapeutic response and safety of the treatment.Methods:A cross-sectional study was de...Objective:To characterize the pediatric population with cutaneous leishmaniasis treated at a research center and to determine the therapeutic response and safety of the treatment.Methods:A cross-sectional study was designed,in which data related to sociodemographic information,history of leishmaniasis,clinical characteristics,treatment,therapeutic response and adverse events were collected from the review of the clinical records.Results:The analysis was conducted in 156 pediatric patients with median age of 10.5(6-14)years.Regarding clinical and therapeutic characteristics,the lesions in these patients were mostly single ulcers,primarily located on the upper and lower extremities.A total of 114 patients were managed at Programa de Estudio y Control de Enfermedades Tropicales(PECET),and 26 of them received more than one treatment.Upon administration of the first therapeutic option,intralesional meglumine antimoniate had a cure rate of 43.18%(19/44 patients),followed by systemic meglumine antimoniate with a cure rate of 40%(8/20)and topical investigational medication with a cure rate of 25%(5/20).The most frequent adverse events were:arthralgia and myalgia for systemic meglumine antimoniate;nausea and vomiting for miltefosine;and local pain,edema,erythema and rash for topical treatment.Conclusions:Although more prospective studies are needed to generate evidence-based recommendations and management protocols,miltefosine appears to be a favorable,safe and well-tolerated therapeutic option for the pediatric population.Despite the high percentage of loss to follow-up,the success achieved in pediatric patients with local treatments suggests that local therapies could also be considered for managing this condition in this population.展开更多
Background Transcatheter Aortic Valve Implantation(TAVI)has changed the treatment paradigm of the aortic stenosis(AS).It has become the treatment of choice in patients with symptomatic AS and surgical high risk,and a ...Background Transcatheter Aortic Valve Implantation(TAVI)has changed the treatment paradigm of the aortic stenosis(AS).It has become the treatment of choice in patients with symptomatic AS and surgical high risk,and a valid alternative to surgical aortic valve replacement in patients with low and medium surgical risk.Despite numerous evidence on clinical results,indications and benefits,only a few studies analyse it from patient's perspective and the impact of TAVI on them.The objective of this study is to evaluate the experience of patients undergoing TAVI.Methods Cross-sectional,descriptive observational study in two Spanish hospitals,with a establish Nurse TAVI program,with100 patients undergoing TAVI.A specific questionnaire was designed(VALVEX questionnaire)and a pilot study was conducted by a multidisciplinary team of doctors,nurses and patients.The questionnaire was given to patients at 30 days after TAVI procedure during the follow up at the TAVI nurse clinic.Results The study demonstrated a mean satisfaction of 9 for the TAVI program,with 96%of patients that would recommend TAVI to other patients.Patients scored a high satisfaction on the information received prior to the procedure.During the procedure and admission,the satisfaction was high in relation to the care received.During the follow up,satisfaction was high in relation to the role of the TAVI nurse,for the information and continuation of care during the procedure,in reducing anxiety,organising their admission and understanding the process.However,questions with less scores were related to hospital catering,delay between diagnosed and treatment,and patient decision-making process.Conclusion The evaluation of patient experience allows us to improve the information given to the patient during their TAVI process and it can also allow patients to be more relax,aware and prepared for the procedure.Continuous follow up enables monitoring of patient recovery and helps to discuss any doubts improving patient's satisfaction.The use of PREMs and PROMs associated to TAVI pathway combined with an active participation of the patient on the design of the questionnaire is essential for keeping the patient in the centre of the TAVI pathway.展开更多
The development of clinical candidates that modify the natural progression of sporadic Parkinson's disease and related synucleinopathies is a praiseworthy endeavor,but extremely challenging.Therapeutic candidates ...The development of clinical candidates that modify the natural progression of sporadic Parkinson's disease and related synucleinopathies is a praiseworthy endeavor,but extremely challenging.Therapeutic candidates that were successful in preclinical Parkinson's disease animal models have repeatedly failed when tested in clinical trials.While these failures have many possible explanations,it is perhaps time to recognize that the problem lies with the animal models rather than the putative candidate.In other words,the lack of adequate animal models of Parkinson's disease currently represents the main barrier to preclinical identification of potential disease-modifying therapies likely to succeed in clinical trials.However,this barrier may be overcome by the recent introduction of novel generations of viral vectors coding for different forms of alpha-synuclein species and related genes.Although still facing several limitations,these models have managed to mimic the known neuropathological hallmarks of Parkinson's disease with unprecedented accuracy,delineating a more optimistic scenario for the near future.展开更多
文摘Heart transplantation(HTx)is a life-saving procedure for patients with end-stage heart failure and has undergone remarkable advancements since the first succe-ssful transplant in 1967.The introduction of cyclosporine in the 1970s significantly improved patient outcomes,leading to a global increase in transplants,including in India,where the practice has grown despite initial challenges.This review pro-vides an extensive overview of HTx,focusing on current practices,technological advancements,and the ongoing challenges the field faces today.It explores the evolution of surgical techniques,such as minimally invasive and robotic-assisted procedures,and the management of posttransplant rejection through tailored immunosuppressive strategies,including new monoclonal antibodies and perso-nalized therapies.The review also highlights emerging innovations such as mechanical circulatory support devices and xenotransplantation as potential solutions to donor shortages while acknowledging the ethical and logistical challenges these approaches entail.Furthermore,the analysis delves into the implications of using extended-criteria donors and the role of multidisciplinary teams in evaluating absolute and relative contraindications.Despite the progress made,the persistent issues of organ scarcity and ethical concerns underscore the need for ongoing research and innovation to further enhance the efficacy,safety,and accessibility of HTx.
基金supported by the Grant PID2021-126715OB-IOO financed by MCIN/AEI/10.13039/501100011033 and"ERDFA way of making Europe"by the Grant PI22CⅢ/00055 funded by Instituto de Salud CarlosⅢ(ISCⅢ)+6 种基金the UFIECPY 398/19(PEJ2018-004965) grant to RGS funded by AEI(Spain)the UFIECPY-396/19(PEJ2018-004961)grant financed by MCIN (Spain)FI23CⅢ/00003 grant funded by ISCⅢ-PFIS Spain) to PMMthe UFIECPY 328/22 (PEJ-2021-TL/BMD-21001) grant to LM financed by CAM (Spain)the grant by CAPES (Coordination for the Improvement of Higher Education Personnel)through the PDSE program (Programa de Doutorado Sanduiche no Exterior)to VSCG financed by MEC (Brazil)
文摘The brain is the most complex human organ,and commonly used models,such as two-dimensional-cell cultures and animal brains,often lack the sophistication needed to accurately use in research.In this context,human cerebral organoids have emerged as valuable tools offering a more complex,versatile,and human-relevant system than traditional animal models,which are often unable to replicate the intricate architecture and functionality of the human brain.Since human cerebral organoids are a state-of-the-art model for the study of neurodevelopment and different pathologies affecting the brain,this field is currently under constant development,and work in this area is abundant.In this review,we give a complete overview of human cerebral organoids technology,starting from the different types of protocols that exist to generate different human cerebral organoids.We continue with the use of brain organoids for the study of brain pathologies,highlighting neurodevelopmental,psychiatric,neurodegenerative,brain tumor,and infectious diseases.Because of the potential value of human cerebral organoids,we describe their use in transplantation,drug screening,and toxicology assays.We also discuss the technologies available to study cell diversity and physiological characteristics of organoids.Finally,we summarize the limitations that currently exist in the field,such as the development of vasculature and microglia,and highlight some of the novel approaches being pursued through bioengineering.
基金supported by the Tomsk State University Development Program(《Priority-2030》)the Basic Project of the Federal Research Center of the Scientific Center,no.FWES-2024-0023the Russian Science Foundation(project No.23-14-20015)。
文摘The growth,survival,and mortality of conifer species in response to the hydrothermal regime have received considerable attention.It is expected that the highest sensitivity of trees to the warming-drying climate will occur mainly at the edges of the species ranges.We focused on the responses to climate change of the drought-resistant larch(Larix sibirica)and the moisture-sensitive Siberian pine(Pinus sibirica)along the elevation gradient in the Tannu-Ola Ridge,the southern margin where those two species coexist in Siberia by using satellite data(MODIS,Landsat,and microwave),the indexes of gross(GPP)and net(NPP)primary productivity,and tree radial growth index(GI).We found that since the warming restart in the 2000s,the area of larch-dominated forests increased by~150%while the area of pine-dominated forests decreased by~10%.The Siberian pine has retreated at low elevations(<1800 m)and increased its area at higher ones.In contrast,the area of larch stands increased in both the uphill and downhill directions.Birch(Betula spp.)also increased its area at low elevations(about+120%).Since 2001,the forested area increased by~5%.A shrubification,i.e.,an increase in the area of shrubs,was observed at high elevations.The uphill rate of timberline and shrubline migration was about 0.3 m/a.Since the 2000s,vegetation NPP has increased by 13%.A notable correlation between NPP and the GI of larch and pine was found(r=0.5-0.7).At lower elevations,NPP positively correlated with precipitation and soil moisture,while air temperature and VPD(vapor pressure deficit)increase inhibited productivity.At high elevations,the effects of these variables on productivity reversed.The continuous decline of the Siberian pine forest indicates an inevitable retreat of this species at low elevations and its replacement by larch and birch.
基金would like to thank the Deanship of Graduate Studies and Scientific Research at Qassim University for financial support(QU-APC-2025).
文摘Automated and accurate movie genre classification is crucial for content organization,recommendation systems,and audience targeting in the film industry.Although most existing approaches focus on audiovisual features such as trailers and posters,the text-based classification remains underexplored despite its accessibility and semantic richness.This paper introduces the Genre Attention Model(GAM),a deep learning architecture that integrates transformer models with a hierarchical attention mechanism to extract and leverage contextual information from movie plots formulti-label genre classification.In order to assess its effectiveness,we assessmultiple transformer-based models,including Bidirectional Encoder Representations fromTransformers(BERT),ALite BERT(ALBERT),Distilled BERT(DistilBERT),Robustly Optimized BERT Pretraining Approach(RoBERTa),Efficiently Learning an Encoder that Classifies Token Replacements Accurately(ELECTRA),eXtreme Learning Network(XLNet)and Decodingenhanced BERT with Disentangled Attention(DeBERTa).Experimental results demonstrate the superior performance of DeBERTa-based GAM,which employs a two-tier hierarchical attention mechanism:word-level attention highlights key terms,while sentence-level attention captures critical narrative segments,ensuring a refined and interpretable representation of movie plots.Evaluated on three benchmark datasets Trailers12K,Large Movie Trailer Dataset-9(LMTD-9),and MovieLens37K.GAM achieves micro-average precision scores of 83.63%,83.32%,and 83.34%,respectively,surpassing state-of-the-artmodels.Additionally,GAMis computationally efficient,requiring just 6.10Giga Floating Point Operations Per Second(GFLOPS),making it a scalable and cost-effective solution.These results highlight the growing potential of text-based deep learning models in genre classification and GAM’s effectiveness in improving predictive accuracy while maintaining computational efficiency.With its robust performance,GAM offers a versatile and scalable framework for content recommendation,film indexing,and media analytics,providing an interpretable alternative to traditional audiovisual-based classification techniques.
文摘The Rh blood group system,especially the D antigen,is crucial in transfusion medicine and obstetrics.Weak D phenotypes,caused by mutations in the Rhesus D antigen(RhD)blood group(RHD)gene,result in reduced antigen expression,posing challenges in serological testing and clinical management.Variability in detection methods leads to inconsistent results,making accurate classification difficult.Molecular techniques like polymerase chain reaction and DNA sequencing have significantly improved the identification of weak D variants,offering more reliable transfusion strategies and reducing the risk of alloimmunization.However,challenges such as lack of standardized protocols,cost constraints,and population-specific variations remain.In obstetrics,proper management of pregnant women with weak D is essential to prevent hemolytic disease of the fetus and newborn.Non-invasive prenatal testing using cell-free fetal DNA shows promise in predicting RhD incompatibility and minimizing unnecessary Rh immune globulin administration.Future advancements in highthroughput genotyping and discovery of novel RHD alleles could enhance RhD testing accuracy and efficiency.Standardizing RHD genotyping and adopting genotype-based management strategies for Rh immune globulin therapy and red blood cell transfusions will improve patient safety and clinical outcomes.This review examines the molecular basis,challenges,and future prospects in weak D phenotype management.
基金supported by grants from the Beijing Hospitals Authority Youth Program (12022B4010)BTCH Young Talent En-lightenment Program (2024QMRC24)CAMS Innovation Fund for Medical Sciences (2019-I2M-5–056)。
文摘Extracorporeal liver surgery(ELS), also known as liver autotransplantation, is a hybrid(cross-fertilized) surgery incorporating the technical knowledge from extreme liver and transplant liver surgeries, and recently became more embraced and popularized among leading centers. ELS could be summarized into three major categories, namely, ex-situ liver resection and autotransplantation(ELRA), ante-situm liver resection and autotransplantation(ALRA) and auxiliary partial liver autotransplantation(APLA). The successful development of ELS during the past 37 years is definitely inseparable from continuous effort s done by Chinese surgeons and researchers. Especially, the precision liver surgery paradigm has allowed to transform ELS into a modularized, more simplified, and standardized surgery, to upgrade surgical skills, to improve peri-operative outcome and long-term survival, to increase the capability of surgeons to select more complex diseases and to expand the level of medical service to the population. This review highlights the Chinese contributions to the field of ELS, focusing thereby on features of different surgical types, technical innovations, disease selection and surgical indication, patient prognosis and future perspectives.
文摘Global climate change has become one of the most pressing challenges of the 21st century.As anthropogenic CO_(2) emissions from fossil fuel consumption and industrial processes continue to disrupt Earth’s carbon cycle,atmospheric CO_(2) concentrations have reached unprecedented levels-exceeding 420 parts per million(ppm)in 2023 compared to pre-industrial 280 ppm.This rapid accumulation of greenhouse gases has resulted in measurable con-sequences including rising global temperatures,ocean acidifica-tion,and increased frequency of extreme weather events.
文摘Lynch syndrome(LS),also known as hereditary non-polyposis colorectal cancer(HNPCC),is an inherited condition associated with a higher risk of colorectal cancer(CRC)and other cancers.It is caused by germline mutations in DNA mismatch repair(MMR)genes,including MLH1,MSH2,MSH6 and PMS2.These mutations lead to microsatellite instability(MSI)and defective DNA repair mechanisms,resulting in increased cancer risk.Early detection of LS is crucial for effective management and cancer prevention.Endoscopic surveillance,particularly regular colonoscopy,is recommended for individuals with LS to detect CRC at early stages.Additionally,universal screening of CRC for MMR deficiency can help identify at-risk individuals.Genetic counseling plays a valuable role in LS by guiding patients and their families in understanding the genetic basis,making informed decisions regarding surveillance and prevention,and offering reproductive options to reduce the transmission of pathogenic variants of the offspring.The aim of this review is to outline current strategies for the diagnosis,surveillance,and management of LS,with a focus on the role of genetic counseling,endoscopic screening,and emerging therapeutic approaches to mitigate cancer risk in affected individuals.
文摘In this letter,a commentary on the article by Xu et al has been provided.Gastrointestinal stomal tumours(GISTs)are rare tumours that originate commonly in stomach(60%-70%)and small intestine(30%-40%).The course of treatment especially oesophageal GIST is very complex and hard to diagnose because of limited availability of pathological and clinical data.Endoscopic resection(ER)is a minimally invasive approach for removing tumours from the oesophagus and digestive system that does not require open surgery and is especially successful for very small and low-risk GIST.A retrospective exami-nation of 32 patients treated with ER between 2012 and 2023 was conducted to analyse clinical and pathological characteristics,effectiveness of therapy,and long-term prognosis.The findings demonstrate en bloc resection was achieved in 96.9%of cases with an R0 resection rate of 75%with a median size of tumour was approximately 2.12 cm.Post-surgery complication like hydrothorax,post-endoscopic submucosal dissection electrocoagulation syndrome occurred in about 25%of cases which later go resolved by conservative treatment.Recurrence of GIST was approximately 9.4%primarily in high-risk cases.ER should be widely adopted in clinical practise preferably for managing low-risk oesophageal GIST because of its high success rate,low recurrence rates and excellent survival results,ensuring better patient prognosis.
基金the Canadian NRCan OERD Energy Innovation Programthe Natural Sciences and Engineering Research Council of Canada,and the Carbon Solution Program for their financial support.
文摘The pursuit of alternative fuel generation technologies has gained momentum due to the diminishing reserves of fossil fuels and global warming from increased CO_(2)emission.Among the proposed methods,the hydrogenation of CO_(2)to produce marketable carbon-based products like methanol and ethanol is a practical approach that offers great potential to reduce CO_(2)emissions.Although significant volumes of methanol are currently produced from CO_(2),developing highly efficient and stable catalysts is crucial for further enhancing conversion and selectivity,thereby reducing process costs.An in-depth examination of the differences and similarities in the reaction pathways for methanol and ethanol production highlights the key factors that drive C-C coupling.Identifying these factors guides us toward developing more effective catalysts for ethanol synthesis.In this paper,we explore how different catalysts,through the production of various intermediates,can initiate the synthesis of methanol or ethanol.The catalytic mechanisms proposed by spectroscopic techniques and theoretical calculations,including operando X-ray methods,FTIR analysis,and DFT calculations,are summarized and presented.The following discussion explores the structural properties and composition of catalysts that influence C-C coupling and optimize the conversion rate of CO_(2)into ethanol.Lastly,the review examines recent catalysts employed for selective methanol and ethanol production,focusing on single-atom catalysts.
基金The University of Winnipeg and The University of Winnipeg Foundation contributed funding to this research.
文摘Variation in the vocal behavior of nonhuman vertebrates includes graded transitions and more dramatic changes.Wapiti males produce a reproductive bugle that has a fundamental frequency that surpasses 2,000 Hz with evidence of biphonation and other nonlinear phenomena.Here,we analyze the acoustic structure of captive wapiti vocalizations to compare the male bugle with 3 categories of distress vocalizations:neonate distress(capture)calls,calf isolation calls,and adult female isolation calls.These 4 high-arousal call categories serve a common general function in recruiting conspecifics but occur in different behavioral contexts(capture,isolation,reproduction).Our goal was to distinguish characteristics that vary in graded steps that may correspond to an animal’s age or size from characteristics that are unique to the bugle.Characteristics of the high and loud fundamental(G0)varied in an age/size-graded manner with a decrease in minimum G0,an increase in the maximum and range of G0,with no evidence of sex differences.The nonlinear phenomena of deterministic chaos,biphonation,and frequency jumps were present in all 4 call categories and became more common from the distress vocalizations of neonates to calves to adult females to the male bugle.Two temporal characteristics sharply distinguished the bugle from the 3 categories of distress vocalizations:these included a prolonged call duration and a maximum G0 that occurred much later in the call for the bugle than for distress vocalizations.Our results suggest that distress vocalizations of different age groups and the reproductive bugle of wapiti share a high G0,with age/size-graded changes in G0 and nonlinear phenomena,but differ sharply in temporal characteristics.
文摘Selfishness,understood as excessive focus on the self,appears to be a predominant feature of contemporary culture.While the degree of self-focus is adaptive for survival and decision-making,self-rigidity has been associated with significant psychological,interpersonal,and social costs.Throughout history,philosophers,religious leaders,and social activists have promoted a“hypo-egoic”way of being,characterized by reduced self-fixation and greater openness to others.However,a key question arises:How can one cultivate a more flexible and interdependent perspective on the self?Deconstructive meditations are a group of contemplative practices that aim to dismantle self-rigidity by exploring perception,cognition,and emotion.Their central mechanism is self-inquiry,an experiential process that involves directly observing patterns of the self,questioning the solidity of identity,and developing new ways to relate to experience.From the perspective of contemplative neuroscience,these practices have been shown to reduce selfnarrative identification and promote psychological flexibility.Despite their potential,empirical research on deconstructive meditations remains limited and requires further investigation.This article reviews the essential findings on practices,their connection to psychotherapy,and their potential therapeutic applications.Finally,their clinical implications are discussed along with future research directions to validate their impact on mental health.
文摘BACKGROUND The rising global prevalence of gastroesophageal reflux disease(GERD)has been closely linked to lifestyle changes driven by globalization.GERD imposes a substantial public health burden,affecting quality of life and leading to potential complications.Early intervention through lifestyle modification can prevent disease onset;however,there is a lack of effective risk prediction models that emphasize primary prevention.AIM To develop and validate a GERD Risk Scoring System(GRSS)aimed at identifying high-risk individuals and promoting primary prevention strategies.METHODS A 45-item questionnaire encompassing major lifestyle and demographic risk factors was developed and validated.It was administered to healthy controls and GERD patients.Two regression models-one using continuous variables and another using categorized variables-were used to develop a computational prediction equation and a clinically applicable scoring scale.An independent validation cohort of 355 participants was used to assess model performance in terms of discrimination(C-index),calibration,sensitivity,specificity,internal consistency(Cronbach's alpha),and test-retest reliability(intraclass correlation coefficient,Bland-Altman analysis).RESULTS Significant associations were observed between GERD and key lifestyle factors.The derived GRSS equation and scoring scale demonstrated strong discriminative ability,with high sensitivity and specificity.The scoring system exhibited excellent internal consistency(Cronbach’s alpha)and strong test-retest reliability.The C-index indicated excellent predictive accuracy in both derivation and validation cohorts.CONCLUSION GRSS offers a novel and validated approach to GERD risk prediction,combining a robust equation for digital applications and a practical scale for clinical use.Its ability to accurately identify at-risk individuals supports a paradigm shift toward primary prevention,underscoring its significance in addressing the growing burden of GERD at the population level.
基金the Ontario Ministry of Agriculture,Food and Rural Affairs,Canada,who supported this project by providing updated soil information on Ontario and Middlesex Countysupported by the Natural Science and Engineering Research Council of Canada(No.RGPIN-2014-4100)。
文摘Conventional soil maps(CSMs)often have multiple soil types within a single polygon,which hinders the ability of machine learning to accurately predict soils.Soil disaggregation approaches are commonly used to improve the spatial and attribute precision of CSMs.The approach disaggregation and harmonization of soil map units through resampled classification trees(DSMART)is popular but computationally intensive,as it generates and assigns synthetic samples to soil series based on the areal coverage information of CSMs.Alternatively,the disaggregation approach pure polygon disaggregation(PPD)assigns soil series based solely on the proportions of soil series in pure polygons in CSMs.This study compared these two disaggregation approaches by applying them to a CSM of Middlesex County,Ontario,Canada.Four different sampling methods were used:two sampling designs,simple random sampling(SRS)and conditional Latin hypercube sampling(cLHS),with two sample sizes(83100 and 19420 samples per sampling plan),both based on an area-weighted approach.Two machine learning algorithms(MLAs),C5.0 decision tree(C5.0)and random forest(RF),were applied to the disaggregation approaches to compare the disaggregation accuracy.The accuracy assessment utilized a set of 500 validation points obtained from the Middlesex County soil survey report.The MLA C5.0(Kappa index=0.58–0.63)showed better performance than RF(Kappa index=0.53–0.54)based on the larger sample size,and PPD with C5.0 based on the larger sample size was the best-performing(Kappa index=0.63)approach.Based on the smaller sample size,both cLHS(Kappa index=0.41–0.48)and SRS(Kappa index=0.40–0.47)produced similar accuracy results.The disaggregation approach PPD exhibited lower processing capacity and time demands(1.62–5.93 h)while yielding maps with lower uncertainty as compared to DSMART(2.75–194.2 h).For CSMs predominantly composed of pure polygons,utilizing PPD for soil series disaggregation is a more efficient and rational choice.However,DSMART is the preferable approach for disaggregating soil series that lack pure polygon representations in the CSMs.
基金supported by National Institutes of Health R03DE027492 to Shareef Dabdoubsupported by National Institutes of Health,project number 7R01DE027857-06supported by National Institutes of Health R56DE033913 awarded to Purnima Kumar.
文摘Dental implants have restored masticatory function to over 100000000 individuals,yet almost 1000000 implants fail each year due to peri-implantitis,a disease triggered by peri-implant microbial dysbiosis.Our ability to prevent and treat peri-implantitis is hampered by a paucity of knowledge of how these biomes are acquired and the factors that engender normobiosis.Therefore,we combined a 3-month interventional study of 15 systemically and periodontally healthy adults with whole genome sequencing,finescale enumeration and graph theoretics to interrogate colonization dynamics in the pristine peri-implant sulcus.We discovered that colonization trajectories of implants differ substantially from adjoining teeth in acquisition of new members and development of functional synergies.Source-tracking algorithms revealed that this niche is initially seeded by bacteria trapped within the coverscrew chamber during implant placement.These pioneer species stably colonize the microbiome and exert a sustained influence on the ecosystem by serving as anchors of influential hubs and by providing functions that enable cell replication and biofilm maturation.Unlike the periodontal microbiome,recruitment of new members to the peri-implant community occurs on nepotistic principles.Maturation is accompanied by a progressive increase in anaerobiosis,however,the predominant functionalities are oxygen-dependent over the 12-weeks.The peri-implant community is easily perturbed following crown placement,but demonstrates remarkable resilience;returning to pre-perturbation states within three weeks.This study highlights important differences in the development of the periodontal and peri-implant ecosystems,and signposts the importance of placing implants in periodontally healthy individuals or following the successful resolution of periodontal disease.
文摘Aortic regurgitation(AR)poses distinct challenges in interventional cardiology,necessitating novel approaches for treatment.This editorial examined the evolving landscape of transcatheter aortic valve replacement(TAVR)as an alternative therapeutic strategy for AR,particularly in patients deemed high risk for surgery.We explored the anatomical and patho-physiological disparities between AR and aortic stenosis(AS)and elucidates the technical nuances of TAVR procedures in AR pa-tients,emphasizing the need for precise prosthesis positioning and considerations for excessive stroke volume.Additionally,we discussed the safety and efficacy of TAVR compared to SAVR in AR management,drawing insights from recent case series and registry data.Notably,dedicated TAVR devices tailored for AR,such as the J-Valve and JenaValve,demonstrate promising out-comes in reducing residual AR and ensuring procedural success.Conversely,“off-label”TAVR devices,including balloon-ex-pandable and self-expandable platforms,offer feasible alternatives-particularly for large aortic annuli-with favorable device suc-cess rates and low residual AR rates.We highlighted the need for further research,including randomized trials,to delineate the definitive role of TAVR in AR treatment and to address remaining questions regarding device selection and long-term outcomes.In conclusion,TAVR emerges as a viable option for patients with AR,particularly those facing high surgical risks or frailty,with ongoing investigations poised to refine its position in the therapeutic armamentarium.
基金Supported by CONAHCYT Project,No.CF-2023-I-2663Instituto Nacional de Psiquiatría Project,No.NC24208.0(to Pérez-Sánchez G,Pavón L,Sánchez-Huerta K,Maldonado-García JL,Chin-Chan JM,Ponce-Regalado MD,Arreola R,Contis-Montes de Oca A,and Moreno-Lafont MC).
文摘Suicide is defined as the act of a person attempting to take their own life by causing death.Suicide is a complex phenomenon that is influenced by a multitude of factors,including psychosocial,cultural,and religious aspects,as well as genetic,biochemical,and environmental factors.From a biochemical perspective,it is crucial to consider the communication between the endocrine,immune,and nervous systems when studying the etiology of suicide.Several pathologies involve the bidirectional communication between the peripheral activity and the central nervous system by the action of molecules such as cytokines,hormones,and neurotransmitters.These humoral signals,when present in optimal quantities,are responsible for maintaining physiological homeostasis,including mood states.Stress elevates the cortisol and proinflammatory cytokines levels and alter neurotransmitters balance,thereby increasing the risk of developing a psychiatric disorder and subsequently the risk of suicidal behavior.This review provides an integrative perspective about the neurochemical,immunological,and endocrinological disturbances associated with suicidal behavior,with a particular focus on those alterations that may serve as potential risk markers and/or indicators of the state preceding such a tragic act.
文摘Objective:To characterize the pediatric population with cutaneous leishmaniasis treated at a research center and to determine the therapeutic response and safety of the treatment.Methods:A cross-sectional study was designed,in which data related to sociodemographic information,history of leishmaniasis,clinical characteristics,treatment,therapeutic response and adverse events were collected from the review of the clinical records.Results:The analysis was conducted in 156 pediatric patients with median age of 10.5(6-14)years.Regarding clinical and therapeutic characteristics,the lesions in these patients were mostly single ulcers,primarily located on the upper and lower extremities.A total of 114 patients were managed at Programa de Estudio y Control de Enfermedades Tropicales(PECET),and 26 of them received more than one treatment.Upon administration of the first therapeutic option,intralesional meglumine antimoniate had a cure rate of 43.18%(19/44 patients),followed by systemic meglumine antimoniate with a cure rate of 40%(8/20)and topical investigational medication with a cure rate of 25%(5/20).The most frequent adverse events were:arthralgia and myalgia for systemic meglumine antimoniate;nausea and vomiting for miltefosine;and local pain,edema,erythema and rash for topical treatment.Conclusions:Although more prospective studies are needed to generate evidence-based recommendations and management protocols,miltefosine appears to be a favorable,safe and well-tolerated therapeutic option for the pediatric population.Despite the high percentage of loss to follow-up,the success achieved in pediatric patients with local treatments suggests that local therapies could also be considered for managing this condition in this population.
基金funded by a IBYE23_0002 grant supported by Instituto de investigación biom-édica de Salamanca IBSAL,Castilla y León (Spain) and by a GRS 2860/A1/2023 by Gerencia Regional de Salud o f Castilla y León (Spain)。
文摘Background Transcatheter Aortic Valve Implantation(TAVI)has changed the treatment paradigm of the aortic stenosis(AS).It has become the treatment of choice in patients with symptomatic AS and surgical high risk,and a valid alternative to surgical aortic valve replacement in patients with low and medium surgical risk.Despite numerous evidence on clinical results,indications and benefits,only a few studies analyse it from patient's perspective and the impact of TAVI on them.The objective of this study is to evaluate the experience of patients undergoing TAVI.Methods Cross-sectional,descriptive observational study in two Spanish hospitals,with a establish Nurse TAVI program,with100 patients undergoing TAVI.A specific questionnaire was designed(VALVEX questionnaire)and a pilot study was conducted by a multidisciplinary team of doctors,nurses and patients.The questionnaire was given to patients at 30 days after TAVI procedure during the follow up at the TAVI nurse clinic.Results The study demonstrated a mean satisfaction of 9 for the TAVI program,with 96%of patients that would recommend TAVI to other patients.Patients scored a high satisfaction on the information received prior to the procedure.During the procedure and admission,the satisfaction was high in relation to the care received.During the follow up,satisfaction was high in relation to the role of the TAVI nurse,for the information and continuation of care during the procedure,in reducing anxiety,organising their admission and understanding the process.However,questions with less scores were related to hospital catering,delay between diagnosed and treatment,and patient decision-making process.Conclusion The evaluation of patient experience allows us to improve the information given to the patient during their TAVI process and it can also allow patients to be more relax,aware and prepared for the procedure.Continuous follow up enables monitoring of patient recovery and helps to discuss any doubts improving patient's satisfaction.The use of PREMs and PROMs associated to TAVI pathway combined with an active participation of the patient on the design of the questionnaire is essential for keeping the patient in the centre of the TAVI pathway.
基金supported by grants PID2020-120308RB-I00 and PID2023-147802OB-I00 funded by MICIU/AEI/10.13039/501100011033FEDER,UE,by Aligning Science Across Parkinson’s(ref.ASAP-020505)through the Michael J.Fox Foundation for Parkinson’s Research+1 种基金by CiberNed Intramural Collaborative Projects(ref.PI2020/09)by the Spanish Fundación Mutua Madrile?a de Investigación Médica(to JLL)。
文摘The development of clinical candidates that modify the natural progression of sporadic Parkinson's disease and related synucleinopathies is a praiseworthy endeavor,but extremely challenging.Therapeutic candidates that were successful in preclinical Parkinson's disease animal models have repeatedly failed when tested in clinical trials.While these failures have many possible explanations,it is perhaps time to recognize that the problem lies with the animal models rather than the putative candidate.In other words,the lack of adequate animal models of Parkinson's disease currently represents the main barrier to preclinical identification of potential disease-modifying therapies likely to succeed in clinical trials.However,this barrier may be overcome by the recent introduction of novel generations of viral vectors coding for different forms of alpha-synuclein species and related genes.Although still facing several limitations,these models have managed to mimic the known neuropathological hallmarks of Parkinson's disease with unprecedented accuracy,delineating a more optimistic scenario for the near future.
